Issue 4, 2009
From the journal:

Organic & Biomolecular Chemistry

Radiolytic activation of a cytarabine prodrug possessing a 2-oxoalkyl group: one-electron reduction and cytotoxicity characteristics†

Nao Hirata,a   Yusuke Fujisawa,a   Kazuhito Tanabe,*a   Hiroshi Harada,bc   Masahiro Hiraokabc  and  Sei-ichi Nishimoto*a  

* Corresponding authors

a Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Katsura Campus, Kyoto, Japan
E-mail: tanabeka@scl.kyoto-u.ac.jp, nishimot@scl.kyoto-u.ac.jp
Fax: +81-75-383-2501
Tel: +81-75-383-2500

b Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan

c Nano-medicine Merger Education Unit, Kyoto University, Kyoto, Japan

Abstract

An anti-tumour agent of cytarabine (ara-C) was conjugated with a 2-oxopropyl group at the N(4) position to obtain a radiation-activated prodrug (oxo-ara-C) that targeted hypoxic tumour tissues with selective cytotoxicity. The parent anti-tumour agent, ara-C, was confirmed to be released from oxo-ara-Cvia one-electron reduction upon hypoxic X-ray treatment. The prodrug oxo-ara-C had dramatically reduced cytotoxicity against human lung adenocarcinoma A549 cells relative to ara-C because of the effect of 2-oxopropyl substituent. In contrast, X-ray treatment of hypoxic A549 cells containing oxo-ara-C enhanced the cytotoxic effect, indicating that toxic ara-C was preferentially released in hypoxic cellsvia radiolytic one-electron reduction by hydrated electrons (eaq−).

Graphical abstract: Radiolytic activation of a cytarabine prodrug possessing a 2-oxoalkyl group: one-electron reduction and cytotoxicity characteristics

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Article information

DOI
https://doi.org/10.1039/B816194A
Article type
Paper
Submitted
16 Sep 2008
Accepted
11 Nov 2008
First published
17 Dec 2008

Org. Biomol. Chem., 2009,7, 651-654

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Radiolytic activation of a cytarabine prodrug possessing a 2-oxoalkyl group: one-electron reduction and cytotoxicity characteristics

N. Hirata, Y. Fujisawa, K. Tanabe, H. Harada, M. Hiraoka and S. Nishimoto, Org. Biomol. Chem., 2009, 7, 651 DOI: 10.1039/B816194A

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